Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

LIMK1 (P53667) - Overview - Molecular Target Synopsis

Protein


LIMK1, LIM domain kinase 1
Enzyme Classification 2.7.11.1
UniProt P53667

Also Known as LIMK1_HUMAN, LIMK1, LIMK

Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop. LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton. In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation. Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly. Stimulates axonal outgrowth and may be involved in brain development. Isoform 3 has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1). Interacts (via LIM domain) with the cytoplasmic domain of NRG1. Interacts with NISCH. Interacts with RLIM and RNF6 (By similarity). Self-associates to form homodimers (PubMed:10196227). Interacts with HSP90AA1; this interaction promotes LIMK1 dimerization and subsequent transphosphorylation (PubMed:16641196). Interacts with CDKN1C (PubMed:14530263). Interacts with SSH1 (PubMed:15660133). Interacts with ROCK1 (PubMed:10436159, PubMed:10652353). Interacts (via LIM zinc-binding domains) with FAM89B/LRAP25 (via LRR repeat). Forms a tripartite complex with CDC42BPA, CDC42BPB and FAM89B/LRAP25.

5NXC
LIM DOMAIN KINASE 1 (LIMK1) IN COMPLEX WITH PF-00477736
RCSB/PDB
Inspect Structure
See all 3D Structures for LIMK1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: LIMK1 is active in the following subcellular-locations: cell projection, cytoplasm, lamellipodium, nucleus.
GO terms: LIMK1 is active in the following subcellular-locations: cytoplasm, cytosol, focal adhesion, lamellipodium, membrane, neuron projection, nuclear speck, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project LIMK1 has gain in 1 cell-lines, loss in 3 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SF_295, U251, UACC_62

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: SK23, HCC4011, MDST8

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, A549, HUVEC

(see details)

RNA Interference


LIMK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB453, SKBR3. (see details)

3D Structures


For LIMK1 there are:
5 structures (8 chains) solved
5 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


LIMK1 has been screened with 599 compounds (943 bioactivities), 160 compounds have bioactivities that show binding affinity of <= 500nM (175 bioactivities). (see details)